rs13210247

Positions:

• chr6-111601517-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147686.4(TRAF3IP2):​c.-9+4259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 274,980 control chromosomes in the GnomAD database, including 1,437 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (979 hom., cov: 32)
  • Exomes 𝑓: 0.078 (458 hom.)
• Consequence: TRAF3IP2 NM_147686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

TRAF3IP2 (HGNC:1343): (TRAF3 interacting protein 2) This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor family. These factors play a central role in innate immunity in response to pathogens, inflammatory signals and stress. This gene product interacts with TRAF proteins (tumor necrosis factor receptor-associated factors) and either I-kappaB kinase or MAP kinase to activate either NF-kappaB or Jun kinase. Several alternative transcripts encoding different isoforms have been identified. Another transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene. [provided by RefSeq, Aug 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4	c.-9+4259T>C		intron_variant		ENST00000368761.11	NP_679211.2
TRAF3IP2-AS1	NR_034108.1	n.4165A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11	c.-9+4259T>C		intron_variant		1	NM_147686.4	ENSP00000357750	P4
	ENST00000531702.1	n.1643A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15496 AN: 152090 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0515

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0777 AC: 9541 AN: 122772 Hom.: 458 Cov.: 0 AF XY: 0.0776 AC XY: 4908 AN XY: 63238

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0381

Gnomad4 SAS exome AF: 0.0725

Gnomad4 FIN exome AF: 0.0674

Gnomad4 NFE exome AF: 0.0708

Gnomad4 OTH exome AF: 0.0870

GnomAD4 genome AF: 0.102 AC: 15524 AN: 152208 Hom.: 979 Cov.: 32 AF XY: 0.101 AC XY: 7482 AN XY: 74426

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.0599

Gnomad4 NFE AF: 0.0650

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0815 Hom.: 584

Bravo AF: 0.112

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13210247; hg19: chr6-111922720;